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Annals of Hematology Apr 2023There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®),...
There are currently three thrombopoietin receptor agonists (TPO-RAs) approved in Europe for treating patients with immune thrombocytopenia (ITP): romiplostim (Nplate®), eltrombopag (Revolade®), and avatrombopag (Doptelet®). However, comparative clinical data between these TPO-RAs are limited. Therefore, the purpose of this study was to perform a literature review and seek expert opinion on the relevance and strength of the evidence concerning the use of TPO-RAs in adults with ITP. A systematic search was conducted in PubMed and Embase within the last 10 years and until June 20, 2022. A total of 478 unique articles were retrieved and reviewed for relevance. The expert consensus panel comprised ITP senior hematologists from eight countries across Central Europe. The modified Delphi method, consisting of two survey rounds, a teleconference and email correspondence, was used to reach consensus. Forty articles met the relevancy criteria and are included as supporting evidence, including five meta-analyses analyzing all three European-licensed TPO-RAs and comprising a total of 31 unique randomized controlled trials (RCTs). Consensus was reached on seven statements for the second-line use of TPO-RAs in the management of adult ITP patients. In addition, the expert panel discussed TPO-RA treatment in chronic ITP patients with mild/moderate COVID-19 and ITP patients in the first-line setting but failed to reach consensus. This work will facilitate informed decision-making for healthcare providers treating adult ITP patients with TPO-RAs. However, further studies are needed on the use of TPO-RAs in the first-line setting and specific patient populations.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Consensus; COVID-19; Thrombocytopenia; Thrombopoietin; Receptors, Fc; Benzoates; Hydrazines; Recombinant Fusion Proteins
PubMed: 36826482
DOI: 10.1007/s00277-023-05114-8 -
Journal of Xenobiotics Jan 2023Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and... (Review)
Review
Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.
PubMed: 36810430
DOI: 10.3390/jox13010005 -
Autoimmunity Reviews Apr 2023Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recent population-based cohort studies suggest that the incidence of systemic lupus erythematosus (SLE) is increased in patients with immune thrombocytopenic purpura (ITP). We performed a systematic review and meta-analysis to evaluate the development of SLE in patients with ITP.
METHODS
Literature search was performed in PubMed, Web of Science and Cochrane Library for studies published prior to October 2022. Studies were included that reported development of SLE in ITP patients. Forest plot was used to detect overall SLE frequency in ITP and compare risk ratios for SLE development in different ITP subgroups. Study heterogeneity was assessed by using I statistics.
RESULTS
26 eligible studies comprising 14867 ITP patients were included in analysis. 311 ITP patients developed SLE during the follow-up period (range: 1.1-14 years) (2.09%, 95%CI: 1.87-2.33). Relative risk (RR) for developing SLE was significantly higher in female ITP patients (RR: 4.23, 95%CI: 2.52-7.12, p < 0.0001). Anti-nuclear antibody (ANA) was reported in 23 studies, there were 766/4377 ANA positive patients with ITP (17.5%). The risk of SLE development in ANA positive ITP patients was significant (RR: 26.29, 95%CI: 14.45-47.81, p < 0.0001).
CONCLUSIONS
Our study suggests ITP patients are at high risk of developing SLE in future. Pooled data revealed that females and patients with a positive ANA titer are at a significantly high risk of developing SLE.
Topics: Female; Humans; Antibodies, Antinuclear; Incidence; Lupus Erythematosus, Systemic; Purpura, Thrombocytopenic, Idiopathic
PubMed: 36781038
DOI: 10.1016/j.autrev.2023.103297 -
Rheumatology (Oxford, England) Jul 2023Satoyoshi syndrome is a rare multisystem disease of presumed autoimmune aetiology. We carried out a systematic review to evaluate the available evidence to support that...
OBJECTIVES
Satoyoshi syndrome is a rare multisystem disease of presumed autoimmune aetiology. We carried out a systematic review to evaluate the available evidence to support that autoimmune hypothesis.
METHODS
We searched for Satoyoshi syndrome cases in PubMed, the Web of Science and Scopus up to January 2022, using keywords 'Satoyoshi syndrome' or 'Komuragaeri disease'. Data on symptoms, associated autoimmune diseases, presence of autoantibodies and response to treatment were collected.
RESULTS
A total of 77 patients from 57 articles published between 1967 and 2021 were included; 59 patients were women. The mean age at diagnosis was 21.2 years. All cases had painful muscular spasms and alopecia. Frequent manifestations included: diarrhoea, malabsorption, growth retardation, amenorrhoea and bone deformity. Satoyoshi syndrome was associated with other autoimmune diseases: myasthenia gravis, autoimmune thyroiditis, idiopathic thrombocytopenic purpura, atopic dermatitis, bronchial and lupus erythematosus. Autoantibody determinations were performed in 39 patients, of which 27 had positive results. The most frequently detected autoantibodies were ANAs. Other less frequently found autoantibodies were: anti-acetylcholine receptor antibodies, anti-DNA antibodies, antithyroid antibodies, anti-glutamic acid decarboxylase (anti-GAD) and anti-gliadin antibodies. Pharmacological treatment was reported in 50 patients. Most of them improved with CS, immunosuppressants and immunoglobulins, or a combination of these medications.
CONCLUSION
Satoyoshi syndrome is associated with other autoimmune diseases and a variety of autoantibodies. Improvement after CS or other immunosuppressant treatment was observed in 90% of cases. These data support an autoimmune aetiology for Satoyoshi syndrome. More studies including systematic determination of autoantibodies in all patients with Satoyoshi syndrome will help us advance in our understanding of this disease.
Topics: Humans; Female; Young Adult; Adult; Male; Spasm; Alopecia; Autoimmune Diseases; Myasthenia Gravis; Autoantibodies; Immunosuppressive Agents; Diarrhea
PubMed: 36749015
DOI: 10.1093/rheumatology/kead067 -
A 'needle in a haystack': Drug-induced thrombotic thrombocytopenic purpura-Association or causality?British Journal of Haematology May 2023The risk of a drug associated with thrombotic thrombocytopenic purpura (TTP) demonstrating causality is rare, but it is important to keep an open mind of possible...
The risk of a drug associated with thrombotic thrombocytopenic purpura (TTP) demonstrating causality is rare, but it is important to keep an open mind of possible associations. Use of criteria to ascertain causality of drugs that may be related to thrombotic microangiopathies and exclude TTP, may be a useful resource. Commentary on: Schofield et al. Drug-induced thrombotic thrombocytopenic purpura: A systematic review and review of European and North American pharmacovigilance data. Br J Haematol 2023;200:766-773.
Topics: Humans; Purpura, Thrombotic Thrombocytopenic; Thrombotic Microangiopathies; Causality
PubMed: 36661238
DOI: 10.1111/bjh.18651 -
The Journal of International Medical... Jan 2023To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To conduct a meta-analysis assessing the efficacy and safety of cyclosporine-based combinations for primary immune thrombocytopenia (ITP).
METHODS
Randomized controlled clinical trials were collected by systematically searching databases (PubMed®, MEDLINE®, EMBASE, The Cochrane Library, China National Knowledge Infrastructure) from inception to June 2022. All studies included patients with ITP who received cyclosporine-based regimens. We performed comprehensive analyses of the overall response rate (ORR), complete response (CR) rate, partial response (PR) rate, relapse rate, platelet count, and adverse drug reaction (ADR) rate.
RESULTS
Seven studies (n = 418) were ultimately included. According to a fixed-effects model, cyclosporine-based combinations improved the ORR and CR rate and reduced the relapse rate. The ADR rate was not increased in the cyclosporine-based combination group. Cyclosporine-based regimens effectively increased the platelet count. Subgroup analysis illustrated that cyclosporine-based combinations were linked to higher ORRs in both children (odds ratio [OR] = 5.74, 95% confidence interval [CI] = 1.79-18.41) and adults (OR = 5.46, 95% CI = 2.48-12.02) and a higher CR rate in adults (OR = 2.97, 95% CI = 1.56-5.63).
CONCLUSION
Cyclosporine exhibited efficacy in the treatment of ITP without increasing the risk of ADRs.
Topics: Child; Adult; Humans; Purpura, Thrombocytopenic, Idiopathic; Cyclosporine; Platelet Count; Clinical Protocols; Remission Induction
PubMed: 36650914
DOI: 10.1177/03000605221149870 -
Pediatric Blood & Cancer Mar 2023Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children... (Review)
Review
Pediatric immune thrombocytopenia (ITP) is an acquired disorder associated with autoimmune destruction and impairment of platelet production in children. Some children exhibit poor or transient response to ITP-directed treatments and are referred to as having refractory ITP (rITP). There is currently no consensus on the definition of rITP, nor evidence-based treatment guidelines for patients with rITP. After a survey of pediatric ITP experts demonstrated lack of consensus on pediatric rITP, we pursued a systematic review to examine the reported clinical phenotypes and treatment outcomes in pediatric rITP. The search identified 253 relevant manuscripts; following review, 11 studies proposed a definition for pediatric rITP with no consensus amongst them. Most definitions included suboptimal response to medical management, while some outlined specific platelet thresholds to define this suboptimal response. Common attributes identified in this study should be used to propose a comprehensive definition, which will facilitate outcome comparisons of future rITP studies.
Topics: Humans; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Blood Platelets; Treatment Outcome; Consensus
PubMed: 36579787
DOI: 10.1002/pbc.30173 -
Frontiers in Neuroendocrinology Jan 2023Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of...
Hormonal contraception has been widely prescribed for decades. Although safety and efficacy are well-established, much uncertainty remains regarding brain effects of hormonal contraception. We systematically review human and animal studies on the brain effects of hormonal contraception which employed neuroimaging techniques such as MRI, PET and EEG, as well as animal studies which reported on neurotransmitter and other brain biochemical effects. We screened 1001 articles and ultimately extracted data from 70, comprising 51 human and 19 animal studies. Of note, there were no animal studies which employed structural or functional MRI, MRS or PET. In summary, our review shows hormonal contraceptive associations with changes in the brain have been documented. Many questions remain and more studies are needed to describe the effects of hormonal contraception on the brain.
Topics: Humans; Contraceptive Agents; Neuroimaging; Brain; Electroencephalography
PubMed: 36577486
DOI: 10.1016/j.yfrne.2022.101051 -
Acta Haematologica 2023The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim,... (Meta-Analysis)
Meta-Analysis
Efficacy and Incidence of Treatment-Related Adverse Events of Thrombopoietin Receptor Agonists in Adults with Immune Thrombocytopenia: A Systematic Review and Network Meta-Analysis of Randomized Controlled Study.
INTRODUCTION
The aim of the study was to conduct a network meta-analysis to assess the efficacy and incidence of treatment-related adverse events (TRAEs) of eltrombopag, romiplostim, avatrombopag, recombinant human thrombopoietin (rhTPO), and hetrombopag for adult immune thrombocytopenia (ITP).
METHODS
Randomized controlled trials (RCTs) of the five therapies from inception to June 1, 2022, were included. The efficacy outcome was the rate of platelet response, defined as the achievement of platelet counts above 50 × 109/L. Pairwise odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The surface under the cumulative ranking (SUCRA) was used to rank the included therapies for each outcome.
RESULTS
In total, 1,360 participants were analyzed in 14 eligible RCTs. All of the therapies showed a significantly better platelet response than the placebo, and avatrombopag (OR, 7.42; 95% CI: 1.74-31.69) and rhTPO (OR, 3.86; 95% CI: 1.62-9.18) were better than eltrombopag. Regarding TRAEs, no significant differences were found between patients receiving eltrombopag, romiplostim, and avatrombopag. Avatrombopag carried the highest platelet response rate with SUCRA value of 87.5, and carried the least TRAEs risk with SUCRA value of 37.0.
CONCLUSIONS
These findings indicated that avatrombopag appeared to be the optimal choice as the second-line therapy for adult ITP.
Topics: Humans; Adult; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thrombopoietin; Incidence; Network Meta-Analysis; Thrombocytopenia; Hydrazines; Benzoates; Recombinant Fusion Proteins; Receptors, Fc; Thrombopoietin; Randomized Controlled Trials as Topic
PubMed: 36572014
DOI: 10.1159/000528642 -
European Journal of Haematology Apr 2023This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their... (Review)
Review
INTRODUCTION
This systematic review aimed to retrieve patients diagnosed with de novo immune thrombocytopenic purpura (ITP) after COVID-19 immunization to determine their epidemiological characteristics, clinical course, therapeutic strategies, and outcome.
MATERIALS AND METHODS
We conducted the review using four major databases, comprising PubMed, Scopus, Web of Science, and the Cochrane library, until April 2022. A systematic search was performed in duplicate to access eligible articles in English. Furthermore, a manual search was applied to the chosen papers' references to enhance the search sensitivity. Data were extracted and analyzed with the SPSS 20.1 software.
RESULTS
A total of 77 patients with de novo COVID-19 vaccine-associated ITP were identified from 41 studies, including 31 case reports and 10 case series. The median age of patients who developed COVID-19 vaccine-associated ITP was 54 years (IQR 36-72 years). The mRNA-based COVID-19 vaccines, including BNT16B2b2 and mRNA-1273, were most implicated (75.4%). Those were followed by the adenovirus vector-based vaccines, inclusive of ChAdOx1 nCoV-19 and vAd26.COV2.S. No report was found relating ITP to other COVID-19 vaccines. Most cases (79.2%) developed ITP after the first dose of COVID-19 vaccination. 75% of the patients developed ITP within 12 days of vaccination, indicating a shorter lag time compared to ITP after routine childhood vaccinations. Sixty-seven patients (87%) patients were hospitalized. The management pattern was similar to primary ITP, and systemic glucocorticoids, IVIg, or both were the basis of the treatment in most patients. Most patients achieved therapeutic goals; only two individuals required a secondary admission, and one patient who presented with intracranial hemorrhage died of the complication.
CONCLUSIONS
De novo ITP is a rare complication of COVID-19 vaccination, and corresponding reports belong to mRNA-based and adenovirus vector-based vaccines, in order of frequency. This frequency pattern may be related to the scale of administration of individual vaccines and their potency in inducing autoimmunity. The more the COVID-19 vaccine is potent to induce antigenic challenge, the shorter the lag time would be. Most patients had a benign course and responded to typical treatments of primary ITP.
Topics: Adult; Aged; Humans; Middle Aged; ChAdOx1 nCoV-19; COVID-19; COVID-19 Vaccines; Purpura, Thrombocytopenic, Idiopathic; Vaccination
PubMed: 36562217
DOI: 10.1111/ejh.13917